This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Almost 5,000 extremely low birth weight (ELBW, birth weight d1000 g;d2 lbs, 3 ounces) infants per year in the US develop severe intraventricular hemorrhage (IVH) that is associated with mental retardation, cerebral palsy, and learning disabilities. As lifetime care costs in these infants exceed $3 billion, IVH in ELBW infants is a major public health problem. Unfortunately, the incidence of severe IVH in ELBW infants has remained constant over the last decade, and accurately identifying the ELBW infants at highest risk of developing IVH has been difficult. Therefore, the long-term goal of our patient-oriented clinical research is to determine the effects of disturbed physiological phenomena associated with IVH in order to predict those infants most at risk and to develop best care clinical practices that may limit severe brain injury. We hypothesize that reducing alterations and extremes of carbon dioxide, blood pressure, and heart rate, factors that influence cerebral blood flow and cerebral autoregulation in ELBW infants, may mitigate the development of IVH and serve as important predictors of ELBW infants most at risk of developing IVH. This will be investigated through a series of clinical studies that will address: 1) whether normocapnic ventilation vs. traditional hypercapnic ventilation will reduce the develop of severe IVH by shifting the incidence to lower grade or no IVH (randomized controlled trial), 2) whether hypotensive ELBW infants have restored intact cerebral autoregulation or continued pressure-passive cerebral blood flow when blood pressure is normalized, and how the postnatal pattern of development of cerebral autoregulation is altered in hypotensive infants, using our novel continuous physiological monitoring system, and 3) whether altered fractal heart rhythm dynamics will serve as an accurate predictor of impending IVH. We will use our continuous physiological monitoring system developed during our K23 studies to determine cerebral autoregulatory capacity during treatment of hypotension and the developmental pattern of cerebral autoregulation during the first week of life. Heart rhythm dynamics on the first day of life will be determined and its value at a predictor of impending IVH will be evaluated. If successful, our proposed clinical studies will reduce the burden of neurological disease in newborn ELBW infants by developing better care clinical practices and by providing a new accurate predictor of impending IVH, so that high risk infants may be identified and interventions applied to limit the development of IVH.